1. Field of the Invention
The present invention relates to formulations of 6.alpha.-methyl, 17.alpha.-hydroxy-progesterone acetate (medroxyprogesterone acetate or MAP).
2. Description of the Prior Art
MAP was independently synthesized in 1958 by two different research groups. It is a synthetic steroid derived from progesterone and exerts, by oral and intramuscular routes, a progestinic activity.
MAP is also used, at higher doses and by the same administration routes, in cancer treatment. In this therapeutic application however, the oral treatment requires very high doses because of the poor bioavailability of the active drug substance. This characteristic is related to the poor wettability and dissolution of the compound in aqueous and biological media. These properties of the compound control and limit the overall absorptability of the compound.
The wettability and dissolution properties of an active drug substance greatly influence its bioavailability; in many cases very active drugs present a poor absorption profile because of their unfavourable dissolution characteristics.
Usually the reduction of the particle size of the drug and the addition of wetting agents have been factors which have been utilized to overcome these problems, but very frequently they prove to be not effective enough. Therefore much effort has been devoted to develop new formulations or new techniques to achieve improved results.
Considerable research effort has recently opened two new research lines based on the preparation of "solid dispersions" and of "inclusion compounds". In the former approach the drug is molecularly dispersed in the carrier, usually a water-soluble polymer (S. Riegelman, W. L. Chiou No. 987,588 4/1976 Canada), while in the latter approach the drug forms molecular complexes with water-soluble cyclodextrins (J. Szejtli, "Cyclodextrins and their inclusion compounds", Akademia Viado, Budapest 1982). A need therefore continues to exist for an improved form of MAP which increases its bioavailability.